TY - JOUR
AB - Respiratory complex I transfers electrons from NADH to quinone, utilizing the reaction energy to translocate protons across the membrane. It is a key enzyme of the respiratory chain of many prokaryotic and most eukaryotic organisms. The reversible NADH oxidation reaction is facilitated in complex I by non-covalently bound flavin mononucleotide (FMN). Here we report that the catalytic activity of E. coli complex I with artificial electron acceptors potassium ferricyanide (FeCy) and hexaamineruthenium (HAR) is significantly inhibited in the enzyme pre-reduced by NADH. Further, we demonstrate that the inhibition is caused by reversible dissociation of FMN. The binding constant (Kd) for FMN increases from the femto- or picomolar range in oxidized complex I to the nanomolar range in the NADH reduced enzyme, with an FMN dissociation time constant of ~ 5 s. The oxidation state of complex I, rather than that of FMN, proved critical to the dissociation. Such dissociation is not observed with the T. thermophilus enzyme and our analysis suggests that the difference may be due to the unusually high redox potential of Fe-S cluster N1a in E. coli. It is possible that the enzyme attenuates ROS production in vivo by releasing FMN under highly reducing conditions.
AU - Holt, Peter
AU - Efremov, Rouslan
AU - Nakamaru Ogiso, Eiko
AU - Sazanov, Leonid A
ID - 1288
IS - 11
JF - Biochimica et Biophysica Acta - Bioenergetics
TI - Reversible FMN dissociation from Escherichia coli respiratory complex I
VL - 1857
ER -
TY - JOUR
AB - Aiming at the automatic diagnosis of tumors using narrow band imaging (NBI) magnifying endoscopic (ME) images of the stomach, we combine methods from image processing, topology, geometry, and machine learning to classify patterns into three classes: oval, tubular and irregular. Training the algorithm on a small number of images of each type, we achieve a high rate of correct classifications. The analysis of the learning algorithm reveals that a handful of geometric and topological features are responsible for the overwhelming majority of decisions.
AU - Dunaeva, Olga
AU - Edelsbrunner, Herbert
AU - Lukyanov, Anton
AU - Machin, Michael
AU - Malkova, Daria
AU - Kuvaev, Roman
AU - Kashin, Sergey
ID - 1289
IS - 1
JF - Pattern Recognition Letters
TI - The classification of endoscopy images with persistent homology
VL - 83
ER -
TY - JOUR
AB - We developed a competition-based screening strategy to identify compounds that invert the selective advantage of antibiotic resistance. Using our assay, we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram. Treating a tetracycline-resistant population with β-thujaplicin selects for loss of the resistance gene, enabling an effective second-phase treatment with doxycycline.
AU - Stone, Laura
AU - Baym, Michael
AU - Lieberman, Tami
AU - Chait, Remy P
AU - Clardy, Jon
AU - Kishony, Roy
ID - 1290
IS - 11
JF - Nature Chemical Biology
TI - Compounds that select against the tetracycline-resistance efflux pump
VL - 12
ER -
TY - JOUR
AB - We consider Ising models in two and three dimensions, with short range ferromagnetic and long range, power-law decaying, antiferromagnetic interactions. We let J be the ratio between the strength of the ferromagnetic to antiferromagnetic interactions. The competition between these two kinds of interactions induces the system to form domains of minus spins in a background of plus spins, or vice versa. If the decay exponent p of the long range interaction is larger than dÂ +Â 1, with d the space dimension, this happens for all values of J smaller than a critical value Jc(p), beyond which the ground state is homogeneous. In this paper, we give a characterization of the infinite volume ground states of the system, for pÂ >Â 2d and J in a left neighborhood of Jc(p). In particular, we prove that the quasi-one-dimensional states consisting of infinite stripes (dÂ =Â 2) or slabs (dÂ =Â 3), all of the same optimal width and orientation, and alternating magnetization, are infinite volume ground states. Our proof is based on localization bounds combined with reflection positivity.
AU - Giuliani, Alessandro
AU - Seiringer, Robert
ID - 1291
IS - 3
JF - Communications in Mathematical Physics
TI - Periodic striped ground states in Ising models with competing interactions
VL - 347
ER -
TY - JOUR
AB - We give explicit formulas and algorithms for the computation of the Thurston–Bennequin invariant of a nullhomologous Legendrian knot on a page of a contact open book and on Heegaard surfaces in convex position. Furthermore, we extend the results to rationally nullhomologous knots in arbitrary 3-manifolds.
AU - Durst, Sebastian
AU - Kegel, Marc
AU - Klukas, Mirko D
ID - 1292
IS - 2
JF - Acta Mathematica Hungarica
TI - Computing the Thurston–Bennequin invariant in open books
VL - 150
ER -
TY - JOUR
AB - For a graph G with p vertices the closed convex cone S⪰0(G) consists of all real positive semidefinite p×p matrices whose sparsity pattern is given by G, that is, those matrices with zeros in the off-diagonal entries corresponding to nonedges of G. The extremal rays of this cone and their associated ranks have applications to matrix completion problems, maximum likelihood estimation in Gaussian graphical models in statistics, and Gauss elimination for sparse matrices. While the maximum rank of an extremal ray in S⪰0(G), known as the sparsity order of G, has been characterized for different classes of graphs, we here study all possible extremal ranks of S⪰0(G). We investigate when the geometry of the (±1)-cut polytope of G yields a polyhedral characterization of the set of extremal ranks of S⪰0(G). For a graph G without K5 minors, we show that appropriately chosen normal vectors to the facets of the (±1)-cut polytope of G specify the off-diagonal entries of extremal matrices in S⪰0(G). We also prove that for appropriately chosen scalars the constant term of the linear equation of each facet-supporting hyperplane is the rank of its corresponding extremal matrix in S⪰0(G). Furthermore, we show that if G is series-parallel then this gives a complete characterization of all possible extremal ranks of S⪰0(G). Consequently, the sparsity order problem for series-parallel graphs can be solved in terms of polyhedral geometry.
AU - Solus, Liam T
AU - Uhler, Caroline
AU - Yoshida, Ruriko
ID - 1293
JF - Linear Algebra and Its Applications
TI - Extremal positive semidefinite matrices whose sparsity pattern is given by graphs without K5 minors
VL - 509
ER -
TY - JOUR
AB - Voronoi diagrams and Delaunay triangulations have been extensively used to represent and compute geometric features of point configurations. We introduce a generalization to poset diagrams and poset complexes, which contain order-k and degree-k Voronoi diagrams and their duals as special cases. Extending a result of Aurenhammer from 1990, we show how to construct poset diagrams as weighted Voronoi diagrams of average balls.
AU - Edelsbrunner, Herbert
AU - Iglesias Ham, Mabel
ID - 1295
JF - Electronic Notes in Discrete Mathematics
TI - Multiple covers with balls II: Weighted averages
VL - 54
ER -
TY - JOUR
AB - In bright light, cone-photoreceptors are active and colour vision derives from a comparison of signals in cones with different visual pigments. This comparison begins in the retina, where certain retinal ganglion cells have 'colour-opponent' visual responses-excited by light of one colour and suppressed by another colour. In dim light, rod-photoreceptors are active, but colour vision is impossible because they all use the same visual pigment. Instead, the rod signals are thought to splice into retinal circuits at various points, in synergy with the cone signals. Here we report a new circuit for colour vision that challenges these expectations. A genetically identified type of mouse retinal ganglion cell called JAMB (J-RGC), was found to have colour-opponent responses, OFF to ultraviolet (UV) light and ON to green light. Although the mouse retina contains a green-sensitive cone, the ON response instead originates in rods. Rods and cones both contribute to the response over several decades of light intensity. Remarkably, the rod signal in this circuit is antagonistic to that from cones. For rodents, this UV-green channel may play a role in social communication, as suggested by spectral measurements from the environment. In the human retina, all of the components for this circuit exist as well, and its function can explain certain experiences of colour in dim lights, such as a 'blue shift' in twilight. The discovery of this genetically defined pathway will enable new targeted studies of colour processing in the brain.
AU - Maximilian Jösch
AU - Meister, Markus
ID - 1303
IS - 7598
JF - Nature
TI - A neuronal circuit for colour vision based on rod-cone opponency
VL - 532
ER -
TY - JOUR
AB - Resolving patterns of synaptic connectivity in neural circuits currently requires serial section electron microscopy. However, complete circuit reconstruction is prohibitively slow and may not be necessary for many purposes such as comparing neuronal structure and connectivity among multiple animals. Here, we present an alternative strategy, targeted reconstruction of specific neuronal types. We used viral vectors to deliver peroxidase derivatives, which catalyze production of an electron-dense tracer, to genetically identify neurons, and developed a protocol that enhances the electron-density of the labeled cells while retaining the quality of the ultrastructure. The high contrast of the marked neurons enabled two innovations that speed data acquisition: targeted high-resolution reimaging of regions selected from rapidly-acquired lower resolution reconstruction, and an unsupervised segmentation algorithm. This pipeline reduces imaging and reconstruction times by two orders of magnitude, facilitating directed inquiry of circuit motifs.
AU - Maximilian Jösch
AU - Mankus, David
AU - Yamagata, Masahito
AU - Shahbazi, Ali
AU - Schalek, Richard L
AU - Suissa-Peleg, Adi
AU - Meister, Markus
AU - Lichtman, Jeff W
AU - Scheirer, Walter J
AU - Sanes, Joshua R
ID - 1306
IS - 2016JULY
JF - eLife
TI - Reconstruction of genetically identified neurons imaged by serial-section electron microscopy
VL - 5
ER -
TY - JOUR
AB - We prove optimal second order convergence of a modified lowest-order Brezzi-Douglas-Marini (BDM1) mixed finite element scheme for advection-diffusion problems in divergence form. If advection is present, it is known that the total flux is approximated only with first-order accuracy by the classical BDM1 mixed method, which is suboptimal since the same order of convergence is obtained if the computationally less expensive Raviart-Thomas (RT0) element is used. The modification that was first proposed by Brunner et al. [Adv. Water Res., 35 (2012),pp. 163-171] is based on the hybrid problem formulation and consists in using the Lagrange multipliers for the discretization of the advective term instead of the cellwise constant approximation of the scalar unknown.
AU - Brunner, Fabian
AU - Julian Fischer
AU - Knabner, Peter
ID - 1315
IS - 4
JF - SIAM Journal on Numerical Analysis
TI - Analysis of a modified second-order mixed hybrid BDM1 finite element method for transport problems in divergence form
VL - 54
ER -